ths edu acsspring2013

An Introduction to Flow Chemistry and its Benefits:“The Future Of Chemical Synthesis”

Who are we?

• ThalesNano is a technology company that gives chemists tools to perform novel, previously inaccessible chemistry safer, faster, and simpler.

• Market leader: Over 700 customer install base on 6 continents.

• Own chemistry team.• 11 years old-most established flow reactor company.• R&D Top 100 Award Winner.

Catalysis reactor: Modular: H-Cube Pro

H-Cube ProH2 Generation150°C, 100 barHydrogenationSelective C-C coupling

Gas Module12 Extra gases100 bar

Phoenix Module450°CNovel heterocycles

Automated injection & collection.Optimization

Mettler Toledo’s FlowIR™ Instant results

ThalesNano Markets

Agrochemical Food, Cosmetics

PetrochemicalPharmaceuticalBiotech

Catalysis

Discovery Development Production

Why do we need new synthetic techniques?

Any change?

Conventional laboratory, 1900

IT effectivity ca.10,000,000 xInstrumental ca. 100,000 x

Conventional lab,2005:effectivity changed cca. 100 x

Organic Synthesis – Growing Complexity

• 1980’s – 2-3 Steps• 1990’s – 3-4 Steps• Today – 4-8 Steps• Future – 8-50 Steps

Industry Trends NCE

What is the issue with chemical space?

Region covered in a conventional laboratory

At ThalesNano

pressure / bar

Temp

erature / °C

100 200 300

Unexploited chemistry space

-100

0

100

200

300

400

500

Expanding the Range of Reaction Conditions

“prepare what you designed and really want rather than what you can readily synthesize”

To achieve the above goal we need a chemical technology toolbox aiming at acceleration of synthetic problem solving!

Nature Reviews Drug Discovery 11, 355-365 (May 2012)

Safety Issues

Chemical Production and E-Factors in Industry

The push for flow

• This has led companies to look at new techniques to: Cut down on number steps→Lower cost Increase yields→less purification downstream Reduce catalyst screening time Re-examine untouchable chemistries→

novel molecules→competitive edge Automate→more efficient

• Flow is one of these techniques being investigated.

What is flow chemistry and how does it differ to batch?

What is flow chemistry?

Performing a reaction continuously, typically on small scale,

through either a coil or fixed bed reactor.

OR

PumpReactor Collection

Kinetics In Flow Reactors

• In a microfluidic device with a constant flow rate, the concentration of the reactant decays exponentially with distance along the reactor.

• Time in a flask reactor equates with distance in a flow reactor

X

A

dX/dt > 0

dA/dt < 0

Improving Mixing:Speeding UpProcesses

Mixing (batch vs. flow)

Flow reactors can achieve homogeneous mixing and uniform heating in microseconds (suitable for fast reactions)

•Benefits• Safety• No filtration necessary • Enhanced phase mixing

Fixed Bed Mixing: Catalyst System-CatCart®

•Over 100 heterogeneous andImmobilized homogeneous catalysts

10% Pd/C, PtO2, Rh, Ru on C, Al2O3

Raney Ni, Raney CoPearlmans, Lindlars CatalystWilkinson's RhCl(TPP)3

Tetrakis(TPP)palladiumPd(II)EnCat BINAP 30

H-Cube Pro Overview

• HPLC pumps continuous stream of solvent • Hydrogen generated from water electrolysis• Sample heated and passed through catalyst• Up to 150°C and 100 bar. (1 bar=14.5 psi)

NH

O2N

NH

NH2

Hydrogenation reactions: Nitro Reduction Nitrile reduction Heterocycle Saturation Double bond saturation Protecting Group hydrogenolysis Reductive Alkylation Hydrogenolysis of dehydropyrimidones Imine Reduction Desulfurization

Reaction times comparison batch vs. flow

Aldoxim reductionAldehyde reduction

0

5

10

15

20

25

30

t /m

in

Flow

Batch

Hydrogenation in batch vs. flow systems

0

200

400

600

800

1000

1200

t /

min

Alkylation Suzuki-Miyaura Azide synthesis Sonogashirareaction

Flow

Batch

Reactions performed in X-Cube™ vs. batch mode

Cover a much bigger parameter space within a very short period of time

H-Cube® Reaction Examples

N

O

OEt

Ar

NH

O

OEt

Ar

Acetic Acid

20% Pd(OH)2/C, 70 bar, 70oC

70% Yield, 5g

RuO2, 100 C

100 bar, 1 mL/min

99% Conversion

Batch: 200°C, 200 bar, 48 hours

Batch: 150°C, 80 bar, 3 days

Gas Module

• Versatile: Compressed Air, O2, CO, C2H4, SynGas, CH4, C2H6, He, N2, N2O, NO, Ar.

• Fast: Reactions with other gases complete in less than 10 minutes

• Powerful: Up to 100 bar capability.

• Robust: All high quality stainless steel parts.

• Simple: 3 button stand-alone control or via simple touch screen control on H-Cube Pro™.

Problems with Oxidation

Alcohol oxidation: Optimization

100 • Area% of desired product in GC-MS / (100 – Area% of reactant in GC-MS)

General conditions: H-Cube Pro with Gas Module, 50 mL/min oxygen gas, 1 mL/min liquid flow rate (0.05M in acetone, 20 mL sample volume), CatCart: 70mm., 1 % Au/TiO2 (cartridge: 70mm, THS 01639),

Batch ref.: Oxygen; perruthenate modified mesoporous silicate MCM-41 in tolueneT=80°C; 24 h; Bleloch, Andrew; et al. Chemical Communications, 1999 , 8,1907 - 1908

Very fast addition of alcohol to gold surface.Alkoxide formation.

ImprovedTemperatureControl

Miniaturization: Enhanced temperature control Large surface/volume rate

• Volume is equal to the length cubed, while surface area is equal to length squared.

• When the length is shortened, surface-to-volume ratio increases. • Microreactors have surface-to-volume ratio than macroreactors, heat

transfer occurs rapidly in a flow microreactor, enabling precise temperature control.

Yoshida, Green and Sustainable Chemical Synthesis Using FlowMicroreactors, ChemSusChem, 2010

Heating Control

Batch Flow

- Lower reaction volume. - Closer and uniform temperature control

Outcome:

- Safer chemistry.- Lower possibility of exotherm.

- Larger solvent volume. - Lower temperature control.

Outcome:

-More difficult reaction control. - Possibility of exotherm.

Heat In:Enabling New Chemistries

Heat in

Q amount of heat transferredt time takenk conductivity of the materialS surface aread distance between the two endsT1 higher temperature endT2 lower temperature end

Flow reactor

Microwave

Oil Bath

Heat transfer of Microwave, Flow reactor, Oil Bath (Flask)

0 100 200 300 400 500 600 700

0

50

100

150

200

250

300

350

400

T /

°C

t / sec

Heat transfer works two ways allowing rapid and safe control of reactions

Phoenix Flow Reactor: High Temperature

Stainless steel coil(1000 mm i.d.)

Razzaq, T.; Glasnov, T. N.; Kappe, C. O. Eur. J. Org. Chem. 2009, doi:10.1002/ejoc.200900077  

Temperature: RT- 450°C

H-Cube Pro

Phoenix

Phoenix reactor possibilities

Loop Materials - sizes Stainless steel (1 – 32 ml) – up to

450oC and 100bar PTFE coil (4 – 16 ml) – up to

150oC and 20bar Hastelloy (4 – 16 ml) – up to 450oC

and 100bar

Cartridge Reactor types• CatCart (30, 70 mm) – up to

300°C and 100bar• MidiCart – up to 150°C and

100bar• Special high temperature

cartridge – up to 450°C and 100bar

Heterocyclic rings of the future, J. Med. Chem., 2009, 52 (9), pp 2952–2963.

• 3000 potential bicyclic systems unmade• Many potential drug like scaffolds

Why?• Chemists lack the tools to expand into new chemistry space

to access these new compounds.• Time• Knowledge

The quest for novel heterocycles

Gould-Jacobs Cyclization

• Standard benzannulation reaction• Good source of:

• Quinolines• Pyridopyrimidones• Naphthyridines

• Important structural drug motifs

Disadvantages:• Harsh conditions• High b.p. solvents• Selectivity• Solubility

Condensation

Cyclization

Saponification Decarboxylation

methylenemalonic ester

W. A. Jacobs, J. Am. Chem. Soc.; 1939; 61(10); 2890-2895

The nature of the substituents is critical because they increase or decrease the nucleophilicity of the ring:

Electron donating groups increase yields, Electron withdrawing groups decrease yields.

35

Process exploration

Meldrum’s acidic route to pyridopyrimidones and to hydroxyquinolines

Meldrum-savCH(OEt)3

3a-eBatch Flow

1a-e 2a-e

a: R=H, R'=H, X=Nb: R=H, R'=H, X=N,c: R=F, R'=H, X=C(CH3)d: R=H, R'=CN, X=CHe: R=H, R'=OCH3, X=CH

in THF

R

N H 2X

RO

OO

O

NH

X

R' R'

3d (43%) 3e (60%)3a (89%) 3b (60%) 3c (62%)

O

NN

F

N

O

N

N

N

OHOH

NC

OHOH

Cyclization conditions:

a: 300 °C, 160 bar, 0.6 min

b: 300 °C, 100 bar, 0.6 min

c: 360 °C, 100 bar, 1 min

d: 350 °C, 130 bar, 4 min

e: 300 °C, 100 bar, 1.5 min

Lengyel L., Nagy T. Zs., Sipos G., Jones R., Dormán Gy., Ürge L., Darvas F., Tetrahedron Lett., 2012; 53; 738-743

No THF polymerization !

AA

NH2

A

AN

O

O

O

A

A

A

A

F V PD ie thyl k e to m a lo na te N

O

O

O

O

A

AA

NHNH2

AA

A

A

F V PD ie thyl k e to m a lo na teNH

NO

OO

O

AA

A

A NH

N

OO

OA

AA

A

NH2

AA

A

A

F V PD ie thyl k e to m a lo na te

NO

OO

O

AA

A

A

OO

O

NA

A

A

A

New Scaffold Generation

PhoenixNH

O

O

O

O

A

A

A

A

M e ld ru m a c id F V PA

A

A

A NH2A

A

A

ANH

O

O

OO

O

AA

A

A

NH2

M e ld ru m a c id F V P

A

A

A

A

NH2

O

OA

A

NH

A

A

O

AA

A

A

F V PM e ld ru m A c id

OO

O

O

AA

A

A

A

A

A

A

O

5 novel bicyclic scaffolds generated-fully characterized.Many more to follow

HN

N

R

O

R

HO

HN

OR

HN R

Phoenix

T3P, 300C80 bar, THF

Ring closure on aryl NH : key step• Mitsunobu reaction or traditional heating with T3P did not

furnish the bicyclic heterocycle.• Reaction proceeded smoothly in Phoenix reactor at 300oC with

65% yield despite requirement for the cis amide conformer in transition state.

Flow offers options to dead ends.

Heat Out:Improving SafetyOf High EnergyProcesses

Heat Out=Exothermic Chem: in situ generation of reactive intermediates

• In batch the reaction can be controlled by low temperature (it slows down the reaction)• In flow it can be at room temperature applying short residence time

Heat Out

Lithium Bromide Exchange

Batch

Flow

• Batch experiment shows temperature increase of 40°C.• Flow shows little increase in temperature.

Ref: Thomas Schwalbe and Gregor Wille, CPC Systems

Setup of the Ice Cube

Ozone Module generate O3 from O2 100 mL/min, 15 % O3

Cooled Reactor Module – teflon tube or glass chip; -50°C.

Pump Module – Peristaltic or Gear PumpOptional: 1 or 2

Selective Ozonolysis Of Eugenol

Reaction parameters:Reagent flow rate 0.7 mL/minQuench flow rate 1.4 mL/minO3 flow rate 17.5 mL/min (~2 eq.)T -5 °CcEugenol 0.05 McNaBH4

0.05 M

Solvent EtOHResults:Conversion 100 %misolated 326.2 mgmmax. yield 504 mgIsolated yield 65 %Purity of isolated product 98 %

ThalesNano lab based chemistry-unpublished

Nitration in flow

OH

HO OH

OH

NO2

NO2

OHOH

O2N

Molecular Weight: 261,10

Molecular Weight: 126,11

Phloroglucinol

Pump A Pump B Temperature (oC)

Loop size (ml)

Conversion (%) Selectivity (%)

SolutionFlow rate (ml/min) Solution

Flow rate (ml/min)

ccHNO3 0.41g PG/15ml

ccH2SO4 0.4 5 - 10 7 1000 (different products)

1.48g NH4NO3/15ml ccH2SO4 0.7

1g PG/15ml ccH2SO4 0.5 5 - 10 13 100 100

1.48g NH4NO3/15ml ccH2SO4 0.5

1g PG/15ml ccH2SO4 0.5 5 - 10 13 50 80 (20% dinitro)

70% ccH2SO4 30% ccHNO3 0.6

1g PG/15ml ccH2SO4 0.5 5 - 10 13 (3 bar) 100 100

70% ccH2SO4 30% ccHNO3 0.6

1g PG/15ml ccH2SO4 0.5 5 - 10 13 (1 bar) 80

70 (30% dinitro and nitro)

Batch reference: 30ml ccH2SO4, 1g PG, 1.48g NH4NO3, 5-10oC 10 min, Conversion: 91%

ImprovingSelectivity

Flow rate vs. residence time

• Increasing the flow rate decreases the residence time - a tool for selectivity

Reactants

Products

By-products

Traditional Batch Method

Gas inlet

Reactants

Products

By-products

Batch vs. Flow

Better surface interactionControlled residence timeElimination of the products

Flow Method

H-Cube Pro™

0,4 0,6 0,8 1,0 1,2 1,4 1,6 1,8 2,0 2,2

85

90

95

100

105

110

Conversion Selectivity

%

Flow rate / mLmin-1

1% Pt/C (V) catalyst at 0,02 concentration of 4-bromo-nitrobenzene

Conditions: 70 bar, EtOH, 25°C

Selectivity through residence time control

Increase and decrease of residence time on the catalyst cannot be performed in batch.

Catalyst Flow rate mL/min

Residence time / sec

Conc. mol/dm3

Conv. %

Sel. %

IrO2 2 9 0,2 52 69

Re2O7 2 9 0,2 53 73

(10%Rh 1% Pd)/C 2 9 0,2 79 60

RuO2 (activated)2 9 0,2 100 100

1 18 0,2 100 99

0,5 36 0,2 100 98

Ru black 2 9 0,2 100 83

1% Pt/C doped with Vanadium

2 9 0,2 100 96

1 18 0,2 100 93

0,5 36 0,2 100 84

Selective dehydrochlorination

Ar

F

F

Cl Ar

F

F

H Ar

F

H

H Ar

H

H

H

A B C D

Flow rate

(mL/min)

Pressure (bar)

Temperature (oC)

Bubdet Catalyst Amount A (%)

Amount B (%)

Amount C (%)

Amount D (%)

1 20 (∆p:5 bar) 110 50 10% Pd/C 26.7% 61.5% - 7%1 20 (∆p:3 bar) 110 50 1% Pd/C 61,90% 29,40% - 2,50%1 20 (∆p:13

bar)110 50 5% Rh/C 78.9% 5.1% - 9.2%

1 20 (∆p:10 bar)

110 50 5% Pd/C 26.7% 60.9% - 6.7%

1 20 (∆p:5 bar) 110 50 5% Pd/C(S) 25% 63.4% - 6.6%

Objective: Match similar selectivity of 60% but without additives of CsF, S, K2CO3 and PPh3

Selective Suzuki coupling (Cl, Cl)

The conditions were:

1 equivalent of 2,6-dichloroquinoxaline with 1.2 equivalent of o-Tolylboronic acid

Concentration set to 0.02MSolvent: MethanolBase: NaOHAnalytics: GC-MS

N

N Cl

Cl

B

HO OH

N

N ClFlow rate (ml/min)

Pressure TemperatureCatalyst Base

Result

(bar) (oC) LC-MS, 220nm

0.8 20 100 Fibrecat 1007 (70mm) 3 ekv

Conversion: 82%Selectivity: 48%

0.3 20 100 Fibrecat 1007 (70mm) 3 ekv

Conversion: 99%Selectivity: 48%

0.8 20 100Fibrecat 1035

2.5 ekvConversion: 16%

(30mm) Selectivity: 100%

0.8 20 100 Fibrecat 1029 (30mm) 2.5 ekv

Conversion: 18%Selectivity: 100%

0.8 20 100 Fibrecat 1048 (30mm) 2.5 ekv

Conversion: 40%Selectivity: 100%

0.8 20 10010% Pd/C

2.5 ekvConversion: 89%

(30mm) Selectivity: 14%

0.5 20 50Fibrecat 1048

2.5 ekvConversion:17%

(30mm) Selectivity: ~100%

0.5 20 100Fibrecat 1048

2.5 ekvConversion: 35%

(30mm) Selectivity: ~100%

0.2 20 100Fibrecat 1007

2.5 ekvConversion: 93%

(70mm) Selectivity: 73%

0.2 20 100Fibrecat 1007

2.5 ekvConversion: 93%

(70mm) Selectivity: 80%

0.2 20 100Fibrecat 1029

2.5 ekvConversion: 12%

(30mm) Selectivity: 100%

Faster OptimizationAnd Analysis

Enabling faster optimization

• Batch reactions gave 1 results after 4 hours!

H2 / cat.+

diphenyl-acetylene

cis-stilbene

trans-stilbene

1,2-diphenylethane

H2 / cat.

H. H., Horváth; G, Papp; Cs., Csajági; F., Joó; Catalysis Communications; 8; 3; 2007; 442-446

30 40 50 60 70 800

20

40

60

80

diphenylethane cis-stilbene trans-stilbene conversion%

T (0C)

Hydrogenation of diphenylacetylene, one day optimization, %f(T)

• [RuCl2(mTPPMS)2]/Molselect DEAE

• p(H2) = 30 bar, [S] = 0.1 M• Solvent: toluene/ethanol 1/1• 24 experiments in 2 hours.

H. H., Horváth; G, Papp; Cs., Csajági; F., Joó; Catalysis Communications; 8; 3; 2007; 442-446

O-Cube™ – H-Cube® - ReactIR™ ozonolysis of decene

Ozonolysis Quenching withH-Cube®

T = -30 ºC

CSM = 0.02 M (in EtOAc)

O3 excess = 30 %

T = -30 ºC to r.t.

p = 1 bar

Cat: 10 % Pd/C

MettlerFlow IR™

O-Cube and ReactIR are trademarks of ThalesNano Inc. and Mettler Toledo International Inc., respectively, H-Cube is registered trademark of ThalesNano Inc.

H2 10%Pd/C

ThalesNano lab based chemistry-unpublished

Ozonide eluted into cool vial under N2

O-Cube ™ -H-Cube ™ -ReactIR ™ reference IR spectra

Specific absorption:Decene: monosubstituted alkene: 917 cm-1, 999 cm-1 (917 cm-1 selected)Nonanal: carbonyl: 1711 cm-1

decene

nonanal

O-Cube™ -H-Cube® -ReactIR™ monitoring

Results: Full Conversion(GCMS)Purity 97% (NMR), no work up neededYield: 85%

Reaction of SM

Increase in Product

FR reduction

Increase in Product

FR increase

Oxidation followed by inline FlowIR

SM

T= 50°C

T= 65°C

T= 80°C

T= 95°C T= 110°C T= 125°C

vflow= 0.5

vflow= 0.75

vflow= 1vflow= 1.5

vflow= 2

p (bar) T (°C) Vflow (ml/min)

33 50 0.533 65 0.533 80 0.533 95 0.533 110 0.533 125 0.533 125 0.7533 125 133 125 1.533 125 2

OCH3

OH Au-TiO2

acetone / O2OCH3

H

O

OH

OF

FCl

OH

OF

FH

First results: reaction was carried out in batch reaction was followed by Picospin 1H NMR product was identified in the crude reaction mixture purified product was also identified Picospin was tuned to 19F

COOH F2HC-

Hydrodehalogenation followed by Picospin

Solvent H2-source T (°C) t (h) Product

water Zn/HCl 100 5 100%

Automating More Processes

H-Cube Autosampler™

Gilson 271 Liquid Handler 402 single Syringe pump (10 mL) Direct GX injector (Valco) Low-mount fraction collection (Bio-Chem) Septum-piercing needle Static drain wash station Tubes, connectors, fittings

Open vial collectionCollection through probe (into closed vial)

Step 1: Optimization

Step 2: Library Production

Library Deprotection

NH2

NH

53

71

80

60

69

63

81

Yield (%) Iodobenzoicacid

Amine

30

55

88

89

25

80

Yield (%)AmineIodobenzoicacid

53

71

80

60

69

63

81

Yield (%) Iodobenzoicacid

Amine

30

55

88

89

25

80

Yield (%)AmineIodobenzoicacid

NH2

Automated test library synthesis Carbonylation

I

OH

O

NH

NH2

NH2

IOH

ONH

NH2

I

OHO NH

NH

NH2

NH2

NH2

I

OH

OCO

NH

OH

O

N

O++X-CUBE

MultistepSynthesis

Reaction at 0 °C instead of -70 °CMultistep syntheses

X = O, S

Yoshida, ChemSusChem 2012, 5, 339 – 350

Residence time = 3.4 s

MeO

MeO

(±)-oxomaritidine

NH

O

Br

HONMe3N3

N3

HO

MeCN:THF (1:1), 70 oC

O

MeO

OMe

(1)

(2)

catch, react, release

MeO

OMe

N

HO

rt to 55 oC

Ph(nBu)2P

H2OH2 (g)electrolysis

Flow hydrogenation

10% Pd/C, THF

MeO

OMe

NH

HO

O

F3C O

O

CF3

MeO

OMe

N

HO

CF3O

80 oC

NMe3RuO4OH

MeO

OMe

PhI(O2CX3)2rt

NMeO

MeO

CF3

O

OMeOH / H2O (4:1)

NMe3OH

35 oC

I.R. Baxendale, J. Deeley, C.M. Griffith-Jones, S.V. Ley, S. Saaby, G. Tranmer, J. Chem. Soc., Chem. Commun., 2006, 2566.

Flow Synthesis of Oxomaritidine

Faster and Safer Scale up

Continuous Process Advantages

Speed• 50 + times faster reactions

Better Process Yields • The continuous process ensures

greater reproducibility • less out of spec and by-products.

Safety• Dangerous reactions, toxic

intermediates• High pressure • High temperature • Supercritical reactions

Environmental impact, green chemistry

• Greener solvents (SCCO2)• Less hazardous waste:• Lower energy consumption

Cost Benefits• Lower Cost Production • Lower Material costs • Greater material yields are

achieved• Considerable savings in

utility costs. • Space requirements are

significantly lower • Less waste management

and disposal costs • Shorter Development &

Scale-up Time

Regulatory aspects• Fits into the FDA PAT

initiatives

H-Cube Midi™ reactor for scale-up

Kilo Scale

N

OH

OHHO

OH

● Genzyme needed 1.2 kg of Zavesca for an internal study, which was priced at 47K USD per 100 g.

N

OH

OHHO

OH

HN

OH

OHHO

OH

H2 / Pd(OH)2 on C

O

H

Saved~ 500K as opposed to purchasing it. It assayed with higher purity than previous commercial lots. Kilo scale.

Genzyme Chemistry

Number up or Scale Out?

Advantages for both, but scale out too much and lose flow advantages!

Survey Conducted

Small scale: Making processes safer Accessing new chemistry Speed in synthesis and

analysis Automation

Large scale: Making processes safer Reproducibility-less batch

to batch variation Selectivity

Why move to flow?

Survey Conducted

What chemistries?

Difficult to perform chemistries

• Low temperature exothermic reactions• Reactions with gases• Very slow reactions or unaccessible chemistry• Reactions with selectivity issues

Approx. 30% of reactions!

Survey Conducted

What are the major blockers?

• Where do I start?• Literature: Flow chemistry Society• Quick Start Guides

• Solubility issues• Test solvents.

What sets us apart?

ThalesNano focuses on designing reactors around specific chemistrysolutions and where flow can be applied best. We don’t try to applyflow chemistry to everything like our competitors!

Exothermic Reactions

• Safety• New chemistry• Speed

Exothermic Reactions

• Safety• New chemistry• Speed

Endothermic Reactions

• Speed• Green

Endothermic Reactions

• Speed• Green

Reactions with gases

• Safety• Simplicity• Speed• Green

Reactions with gases

• Safety• Simplicity• Speed• Green

Scale up

• Safety• Selectivity• Reproducibility• Speed

Scale up

• Safety• Selectivity• Reproducibility• Speed

Flow University

• Practical Lab Manual• Presentation tutorial• Background notes• Educational Videos

In English In Mandarin Chinese Subtitled

Chemistry Services Clients

"ThalesNano delivered to Koste Biochemicals catalyst screening and reaction optimization services of an uncompromising quality with full analytics performed in record-breaking time. A great team to work with !“-Charles Carey, Co-founder Koste Biochemicals

ComInnex Chemistry Services – Our Sister Company

• Our sister drug discovery service provider.• A leader in chemistry, library and medicinal chemistry services• Track record collaborations with >250 customers in US, EU, and Asia.• >800 focused libraries in past 12 years.• European IP standards• Excellent reputation for customer service.• Advantages:

• Located in heart of Europe, Budapest. • European standards and expertise at competitive prices on your doorstep.• CADD, Biology, and ADMET support possible.• Access to ThalesNano’s full equipment inventory.• Novel heterocycles platform based on innovative proprietary technologies.

Acknowledgements

Thank you for your attention!Any questions?

Booth 821

Some slides reproduced with the permission of the Flow Chemistry Society.